SPELL - S. cerevisiae

Citation	Santos-Pereira JM, Herrero AB, Garcia-Rubio ML, Marin A, Moreno S, Aguilera A. The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability. Genes & development, 2013.
PubMed ID	24240235
Short Description	The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability.
# of Conditions	6
Full Description	Transcription is a major obstacle for replication fork (RF) progression and a cause of genome instability. Part of this instability is mediated by cotranscriptional R loops, which are believed to increase by suboptimal assembly of the nascent messenger ribonucleoprotein particle (mRNP). However, no clear evidence exists that heterogeneous nuclear RNPs (hnRNPs), the basic mRNP components, prevent R-loop stabilization. Here we show that yeast Npl3, the most abundant RNA-binding hnRNP, prevents R-loop-mediated genome instability. npl3Delta cells show transcription-dependent and R-loop-dependent hyperrecombination and genome-wide replication obstacles as determined by accumulation of the Rrm3 helicase. Such obstacles preferentially occur at long and highly expressed genes, to which Npl3 is preferentially bound in wild-type cells, and are reduced by RNase H1 overexpression. The resulting replication stress confers hypersensitivity to double-strand break-inducing agents. Therefore, our work demonstrates that mRNP factors are critical for genome integrity and opens the option of using them as therapeutic targets in anti-cancer treatment.
Tags	mRNA processing, transcription